Evidence map›Paper›PMID 34301768›Full record

ArticleGenes & development2021

Nopp140-chaperoned 2'-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity.

Jonathan Bizarro, Svetlana Deryusheva, Ludivine Wacheul, Varun Gupta, Felix G M Ernst, Denis L J Lafontaine, Joseph G Gall, U Thomas Meier

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Coilin and Cajal bodies.Nucleus (Austin, Tex.) · 2023
    Review
  14. Review
  15. Article
  16. Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Jonathan BizarroAlbert Einstein College of Medicine, Bronx, New York 10461, USA.ORCID 0000-0001-9657-3951
Svetlana DeryushevaCarnegie Institution for Science, Baltimore, Maryland 21218, USA.ORCID 0000-0002-6127-1889
Ludivine WacheulRNA Molecular Biology, Fonds National de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
Varun GuptaAlbert Einstein College of Medicine, Bronx, New York 10461, USA.
Felix G M ErnstRNA Molecular Biology, Fonds National de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.ORCID 0000-0001-5064-0928
Denis L J LafontaineRNA Molecular Biology, Fonds National de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.ORCID 0000-0001-7295-6288
Joseph G GallCarnegie Institution for Science, Baltimore, Maryland 21218, USA.ORCID 0000-0001-9664-6559
U Thomas MeierAlbert Einstein College of Medicine, Bronx, New York 10461, USA.ORCID 0000-0001-6677-2677
Albert Einstein College of Medicine · USUniversité Libre de Bruxelles · BECarnegie Institution for Science · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
THE ORGANIZATION OF ANIMAL CELL NUCLEIR01GM033397 · NIGMS · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · PI GALL, JOSEPH G. · 1985 to 2019
$8.4M
Cellular impact of X-linked dyskeratosis congenitaR01HL136662 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI MEIER, U THOMAS · 2017 to 2020
$2.4M
120kV Transmission Electron Microscope for a Multi-user Microscopy FacilityS10OD016214 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CONDEELIS, JOHN S · 2014 to 2014
$459k
NCI NIH HHS P30 CA013330NHLBI NIH HHS R01 HL136662NIGMS NIH HHS R01 GM033397NIH HHS S10 OD016214
6 · The paper itself

Abstract

Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.

Indexed as

MethylationRNA SplicingCasein Kinase IICholangiocarcinomaCOVID-19 Drug TreatmentHematologic NeoplasmsHumansInterstitial Cells of CajalNuclear ProteinsPhosphoproteinsPhosphorylationRibonucleoproteinsRNA, Small NuclearSpliceosomesCasein Kinase IINOLC1 protein, humanNuclear ProteinsPhosphoproteinsRibonucleoproteinsRNA, Small NuclearCajal bodiescasein kinase 2nuclear organizationphosphorylationpre-mRNA splicingRNA modificationscaRNPssnoRNPssnRNA

Identifiers

PMID34301768
PMCPMC8336889
OpenAlexW3185875052

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.